The overall goals of this proposal are: 1) to determine whether initiation of immunomodulatory therapy early in the course of Crohn's disease alters its natural history; and 2) to prepare the principal investigator for an independent career in clinical investigation in gastroenterology. Crohn's disease is a chronic, idiopathic inflammatory condition of the gastrointestinal tract. The currently accepted strategy of medical therapy for Crohn's disease is a graded, stepwise approach. This strategy is intended to improve symptoms while minimizing exposure to side effects. Immunomodulatory therapies are generally not employed until repeat trials of other medications have failed. This approach is based on assumptions that more effective drugs are inherently more dangerous and that the primary goal of therapy should be alleviation of symptoms. Recent reports provide evidence to contradict both assumptions: 1) there is an extensive safety record with highly effective immunomodulatory agents; and 2) alleviation of symptoms often does not reflect biologic remission of the disease or delay its sequelae. Therefore, we propose that early initiation of immunomodulatory therapy will significantly improve the treated natural history of Crohn's disease over the generally accepted, stepwise approach. To test this hypothesis, the investigator proposes a long-term, randomized, double-blind, placebo-controlled trial of additive therapy with the immunomodulatory agent 6-mercaptopurine versus placebo (standard care) initiated within 12 months of diagnosis. The primary analysis to test this hypothesis will be a comparison of the time to first surgery with up to 3 years of follow-up from initiation of study drug among the two treatment groups. The acronym chosen for this study is NOCIS for "New Onset Crohn's Intervention Study." Retrospective and prospective planning studies, including a short-term randomized, controlled trial, will be performed to finalize details of study design and execution of the proposed long-term trial. Continued involvement in the didactic activities of the MGH Center for the Study of Inflammatory Bowel Disease will further the principal investigator's knowledge in inflammatory bowel disease, while the support of the Clinical Research Program will support the clinical research aspects of this proposal. The principal investigator will also seek advanced training in the design, execution, and analysis of clinical trials in the course of completing a Master of Science in Clinical Epidemiology at the Harvard School of Public Health. The principal investigator seeks to become an independent clinical investigator by completing the didactic and scientific portions of this proposal.